WO2005066120A2 - Procede de synthese asymetrique de derives azetidinone hydroxy-alkyle-substitues ou de leurs intermediaires - Google Patents
Procede de synthese asymetrique de derives azetidinone hydroxy-alkyle-substitues ou de leurs intermediaires Download PDFInfo
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- WO2005066120A2 WO2005066120A2 PCT/IB2004/004281 IB2004004281W WO2005066120A2 WO 2005066120 A2 WO2005066120 A2 WO 2005066120A2 IB 2004004281 W IB2004004281 W IB 2004004281W WO 2005066120 A2 WO2005066120 A2 WO 2005066120A2
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- 0 *c1ccc([C@](CC2=O)*2c(cc2)ccc2N)cc1 Chemical compound *c1ccc([C@](CC2=O)*2c(cc2)ccc2N)cc1 0.000 description 6
- CEHMCYSNMYPBBN-XBMUEBEBSA-N O[C@@H](CCCC(N(C(CO1)c2ccccc2)C1=O)O)c(cc1)ccc1F Chemical compound O[C@@H](CCCC(N(C(CO1)c2ccccc2)C1=O)O)c(cc1)ccc1F CEHMCYSNMYPBBN-XBMUEBEBSA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/06—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D205/08—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/31—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of functional groups containing oxygen only in singly bound form
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D263/18—Oxygen atoms
- C07D263/20—Oxygen atoms attached in position 2
- C07D263/22—Oxygen atoms attached in position 2 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to other ring carbon atoms
Definitions
- Hydroxyalkyl substituted azetidinone derivatives such as ezetimibe, i.e., l-(4- fluorophenyl)-3-(R)-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4(S)-(4-hydroxyphenyl)-2- azetidinone, are useful as hypocholesterolemic agents in the prevention and treatment of atherosclerosis.
- U.S. Patent No. 5,767,115 discloses hydroxy-substituted azetidinones as useful hypocholesterolemic agents in the treatment or prevention of atherosclerosis.
- Culture broth of Zygosaccharomyces bailii ATCC 38924 is disclosed as being useful in stereoselective microbial reduction of 5-(4-fluorobenzoyl)-5-oxopentanoic acid to obtain (5S)-5-(4-fluorophenyl)-5-hydroxypentanoic acid in U.S. Patent No. 5,618,707.
- U.S. Patent Nos. 5,886,171 and 5,856,473 disclose chiral reduction of protected 1-
- FIGURE I U.S. Patent No. 6,207,822 discloses the use of similar reducing agents and chiral catalyst for reduction of 3-[5-(4-fluorophenyl)-5-oxopentanoyl]-4(S)-4-phenyl-l,3- oxazolidin-2-one to 3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4(S)-4-phenyl- 1 ,3- oxazolidin-2-one.
- Ri can be hydroxy or protected hydroxy group
- Q 2 , Q 2 or Q 3 wherein R can be an alkyl, aryl or aralkyl group.
- Ri is hydroxy or a protected hydroxy group and R 2 is an alkyl, aryl or aralkyl group.
- the reduction can be performed in a suitable solvent selected from hydrocarbons, chlorinated hydrocarbons, alkyl ethers, nitriles, dipolar aprotic solvents, cyclic ether or mixtures thereof.
- the cyclic ether can be dioxane, tetrahydrofuran or mixtures thereof.
- the compound of Formula II can be added to (-)-B-chlorodiisopinocampheylborane at a temperature from about -80 °C to about 40 °C.
- the reaction can be carried out at the temperature of from about -80 °C to about 45 °C.
- processes for preparing ezetimibe comprising the step of deprotecting a compound of Formula I wherein Q can be Qi
- the compound of Formula I can be prepared by reducing a compound of Formula ⁇ ,
- Formula II with (-)-B-chlorodiisopinocampheylborane of Formula III.
- Formula III Also provided herein are processes for preparing ezetimibe comprising the steps of a. reacting a compound of Formula I
- P can be a protecting group
- P can be a protecting group
- b reacting the hydroxy-protected (/3-substituted-amino) amide with i) a silylating agent and a fluoride ion catalyst cyclizing agent; ii) a silylating agent and a quaternary ammonium salt of a chiral auxiliary, or iii) a strong non-nucleophilic base, and c. removing the hydroxy protecting group.
- the hydroxy protecting agent can be chloromethylsilane, chlorotrimethylsilane, tert-butyldimethylsilyl chloride, or a mixture thereof.
- the silylating agent can be bistrimethylsilyl acetamide.
- the fluoride ion catalyst cyclizing agent can be tetrabutylammonium fluoride trihydrate.
- the chiral auxiliary can be (4S)-4-phenyl-2- oxazolid none.
- compounds of Formula I can be prepared by reducing a compound of Formula 11,
- Compounds of Formula II, wherein Q represents Qi may be obtained by known process, including, for example, processes disclosed in U.S. Patent Nos. 5,886,171 and 5,856,473, which are incorporated herein by reference.
- compounds of Formula II may be obtained by alkylating (4S)- 1 -(4-fluorophenyl)-4-(4-substituted phenyl) azetidin-2-one with 4-fluorocinnamyl bromide, followed by oxidation.
- Compounds of Formula II, wherein Q represents Q 2 may be obtained by known processes including, for example, processes disclosed in U.S. Patent No. 6,207,822, which is incorporated herein by reference.
- Compounds of Formula II may be obtained by reacting p-fluorobenzoylbutyric acid with pivaloyl chloride and reacting the product with a chiral auxiliary, (4S)-4-phenyl-2-oxazolidinone.
- Compounds of Formula II, wherein Q represents Q 3 may be obtained by esterification of the corresponding acid, which in turn may be prepared by known processes including, for example, processes disclosed in U.S. Patent No. 6,207,822, which is incorporated herein by reference.
- the corresponding acid may be obtained by reacting glutaric anhydride and fluorobenzene in the presence of aluminum chloride.
- (-)-B-chlorodiisopinocampheylborane is commercially available as a solid or a solution in heptane.
- the reaction of compound of Formula II, wherein Q is as defined above, with (-)- B-chlorodiisopinocampheylborane may carried out in the presence of a suitable solvent.
- suitable solvents are inert organic solvents that do not change under the reaction conditions.
- solvents examples include hydrocarbons such as benzene, xylene, toluene, hexane, cyclohexane, heptane and octane; chlorinated hydrocarbons such as methylene chloride, ethylene dichloride and carbon tetrachloride; alkyl ethers such as diethylether, diisopropylether and dimethoxyethane; nitriles such as acetonitrile and benzonitrile; dipolar aprotic solvents such as dimethylsulfoxide and dimethylformamide; cyclic ethers such as dioxane and tetrahydrofuran; and mixtures thereof.
- hydrocarbons such as benzene, xylene, toluene, hexane, cyclohexane, heptane and octane
- chlorinated hydrocarbons such as methylene chloride, ethylene dichloride and carbon
- Formula III at a temperature range of about -80 °C to about 40 °C in a suitable solvent, and in some particular embodiments, the temperature may range from about -40 °C to about 10 °C.
- the reaction of compound of Formula II with (-)-B-chlorodiisopinocampheylborane may carried out at the temperature range of about -80 °C to about 45 °C.
- the reaction may be quenched by adding a dialkanolamine, for example, diethanolamine, dipropanolamine, dibutanolamine or mixtures thereof.
- Compounds of Formula I, wherein Q is as defined above can be converted to ezetimibe, by disclosed methods including, for example, methods disclosed in U.S.
- Formula V which is then reacted with a silylating agent and a fluoride ion catalyst cyclizing agent; a silylating agent and a quaternary ammonium salt of a chiral auxiliary, (4S)-4-phenyl-2- oxazolidinone; or a strong non-nucleophilic base followed by removal of hydroxy protecting group to yield ezetimibe.
- hydroxy protecting group, silylating agent and fluoride ion catalyst cyclizing agent are chlorotrimethylsilane, bistrimethylsilyl acetamide and tetrabutylammonium fluoride trihydrate respectively.
- the chiral delta lactone is then reacted with diphenyl imine of Formula TV in the presence of a strong base.
- the hydrolysis can be carried out in the presence of at least one acid or base.
- acids include organic acids, for example, carboxylic acids (e.g., formic acid, acetic acid, propionic acid or mixture thereof), and inorganic acids, for example, hydrochloric acid, hydrobromic acid or mixtures thereof.
- bases include alkali metal carbonates (e.g., lithium carbonate, sodium carbonate, potassium carbonate, or mixtures thereof) and hydroxides (e.g., sodium hydroxide, potassium hydroxide, or mixtures thereof), hi some embodiments when R 2 is benzyl, hydrogenation in the presence of a metal catalyst (e.g., palladium on carbon and ammonium formate) can be used to form the corresponding acid.
- a metal catalyst e.g., palladium on carbon and ammonium formate
- the cyclization reaction after hydrolysis can be carried out in the presence of an acid or a salt of a weak base to obtain a chiral delta lactone.
- Organic and inorganic acids can be used.
- Suitable acids include hydrochloric, p-toluenesulfonic, acetic, and methanesulfonic acids.
- suitable salts of a weak base include pyridinium p-toluenesulfonate, pyridine hydrobromide or mixtures thereof.
- the cyclization reaction may be carried out at a temperature range from about -20 °C to about 120 °C, from about 0 °C to about 60 °C, and even from about 10 °C to about 40 °C.
- Organic solvents can be used in the cyclization reactions, examples of which include, ethers (e.g., diethyl ether, dibutyl ether, methyl tert-butyl ether, dioxane, tetrahydrofuran or mixtures thereof); chlorinated hydrocarbons (e.g., methylenedichloride, ethylenedichloride or mixtures thereof); esters (e.g., ethyl acetate, isopropyl acetate or mixtures thereof); ketones (e.g., acetone, methylisobutylketone (MD3K) or mixtures thereof); hydrocarbons (e.g., hexane, toluene, xylene or mixtures thereof); acetonitrile; dipolar aprotic solvents (e.g., dimethylformamide, dimethyl sulphoxide, N-methylpyrrolidone, sulfolane or mixtures thereof); or mixtures thereof.
- Example 1 Preparation of (5S)-5-(4-fluorophenyl -5-hvdroxypentanoic acid A solution of methyl 5-(4-fluorophenyl)-5-oxopentanoate (20.57 g, 91.8 mmol) in tetrahydrofuran (42 mL) was added to a stirred suspension of (-)-B- chlorodiisopinocampheylborane (50.07 g, 156.1 mmol) in tetrahydrofuran (50 mL) at a temperature from about -35 °C to -25 °C over 30 minutes. The resulting solution was stirred for 20 hours at -25 °C.
- reaction mixture was quenched with water (43 mL) at -10 ⁇ 2 °C over 10 minutes followed by addition of 5M sodium hydroxide solution (123 mL) at 0 °C over 15 minutes. After about 80 minutes, saturated sodium bicarbonate solution (82 mL) and dichloromethane (133 mL) were added. After stirring at about 20 °C for 15 minutes, the two layers were separated. The aqueous layer was acidified with aqueous 6M hydrogen chloride (25mL) to pH 2.78 and the separated solid was filtered and dried under vacuum to yield (5S)-5-(4-fluoro ⁇ henyl)-5-hydroxypentanoic acid
- the reaction mixture was then stirred for 2 hours at 20°C to 30°C and filtered.
- the precipitate was washed with toluene (500 mL) and the combined filtrate was washed twice with water (400 mL each washing).
- the organic layer was concentrated under vacuum at about 40 °C to about 45 °C and the residue was triturated with hexane (800 mL).
- the hexane solution was decanted and concentrated under vacuum to yield the title product as an oil.
- Example 3 Preparation of l-(4-fluorophenyl)-3(R)-[3-(4-fluorophenyl)-3(S - hydroxypropyl] -4rS -(4-hydroxyphenyl -2-azetidinone (Ezetimibe ' )
- a solution of (-)-B-chlorodiisopinocampheylborane in heptane (46 mL, 60-65%) was added slowly to l-(4-fluorophenyl)-3(R)-[3-oxo-3-(4-fluorophenyl)propyl)]-4-(S)-(4- hydroxyphenyl)-2-azetidinone (20 g, 49 mmol) in tetrahydrofuran (60 mL) at about 5-10 °C.
- the mixture was brought to ambient temperature (about 25-30 °C) and stirred for 6-8 hours until completion of the reduction reaction.
- the mixture was again cooled and diethanolamine (7.7 g) was added at about 5-10 °C and stirred for about 2 hours.
- Solid byproducts were filtered and the filtered cake was washed with tetrahydrofuran (20 mL).
- the filtrate was combined and concentrated on rotary evaporator at about 40 °C.
- the concentrated mass was dissolved in ethyl acetate (120 mL) and shaken twice with 5% aqueous solution of diethanolamine (30 mL each). The ethyl acetate layer was then washed twice with water (20 mL each) and concentrated.
Abstract
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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IN1643DE2003 | 2003-12-30 | ||
IN1643/DEL/2003 | 2003-12-30 |
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WO2005066120A2 true WO2005066120A2 (fr) | 2005-07-21 |
WO2005066120A3 WO2005066120A3 (fr) | 2008-01-17 |
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Cited By (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7470678B2 (en) | 2002-07-05 | 2008-12-30 | Astrazeneca Ab | Diphenylazetidinone derivatives for treating disorders of the lipid metabolism |
US7842684B2 (en) | 2006-04-27 | 2010-11-30 | Astrazeneca Ab | Diphenylazetidinone derivatives possessing cholesterol absorption inhibitor activity |
US7863265B2 (en) | 2005-06-20 | 2011-01-04 | Astrazeneca Ab | 2-azetidinone derivatives and their use as cholesterol absorption inhibitors for the treatment of hyperlipidaemia |
US7871998B2 (en) | 2003-12-23 | 2011-01-18 | Astrazeneca Ab | Diphenylazetidinone derivatives possessing cholesterol absorption inhibitory activity |
US7893048B2 (en) | 2005-06-22 | 2011-02-22 | Astrazeneca Ab | 2-azetidinone derivatives as cholesterol absorption inhibitors for the treatment of hyperlipidaemic conditions |
US7906502B2 (en) | 2005-06-22 | 2011-03-15 | Astrazeneca Ab | 2-azetidinone derivatives as cholesterol absorption inhibitors for the treatment of hyperlipidaemic conditions |
US7956182B2 (en) | 2006-02-16 | 2011-06-07 | Kotobuki Pharmaceutical Co., Ltd. | Process for preparing optically active alcohols |
US8178665B2 (en) | 2005-12-20 | 2012-05-15 | Richter Gedeon Nyrt. | Process for the production of ezetimibe and intermediates used in this process |
US9388440B2 (en) | 2009-04-01 | 2016-07-12 | Mylan Laboratories Limited | Enzymatic process for the preparation of (S)-5-(4-fluoro-phenyl)-5-hydroxy-1morpholin-4-yl-pentan-1-one, an intermediate of Ezetimibe and further conversion to Ezetimibe |
CN107488173A (zh) * | 2016-06-10 | 2017-12-19 | 山东新时代药业有限公司 | 一种依折麦布中间体及其合成方法 |
CN108586373A (zh) * | 2018-06-22 | 2018-09-28 | 苏州市贝克生物科技有限公司 | 依折麦布中间体的合成方法 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5856473A (en) * | 1995-11-02 | 1999-01-05 | Schering Corporation | Process for preparing 1-(4-fluorophenyl)-3(R)-(3(S)-hydroxy-3-( phenyl or 4-fluorophenyl!)-propyl)-4(S)-(4-hydroxyphenyl)-2-azetidinone |
WO2005049592A1 (fr) * | 2003-11-24 | 2005-06-02 | Hetero Drugs Limited | Nouveau procede de preparation d'intermediaire d'ezetimibe |
-
2004
- 2004-12-23 WO PCT/IB2004/004281 patent/WO2005066120A2/fr active Application Filing
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5856473A (en) * | 1995-11-02 | 1999-01-05 | Schering Corporation | Process for preparing 1-(4-fluorophenyl)-3(R)-(3(S)-hydroxy-3-( phenyl or 4-fluorophenyl!)-propyl)-4(S)-(4-hydroxyphenyl)-2-azetidinone |
WO2005049592A1 (fr) * | 2003-11-24 | 2005-06-02 | Hetero Drugs Limited | Nouveau procede de preparation d'intermediaire d'ezetimibe |
Non-Patent Citations (4)
Title |
---|
CHEN ET AL.: "Asymetric Synthesis of Substituted 2-Azaspiro[3.5Ünonan-1-ones: An Enantioselective Synthesis of the Cholesterol Absorption Inhibitor (+)-SCH 54016" JOURNAL OF ORGANIC CHEMISTRY, vol. 61, 1996, pages 8341-8343, XP002335913 * |
FU X ET AL: "Process for preparing Ezetimibe intermediate by an acid enhanced chemo- and enantioselective CBS catalyzed ketone reduction" TETRAHEDRON LETTERS, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 44, no. 4, 20 January 2003 (2003-01-20), pages 801-804, XP004405139 ISSN: 0040-4039 cited in the application * |
RAMACHANDRAN ET AL.: "Selective reductions" JOURNAL OF ORGANIC CHEMISTRY, vol. 67, 2002, pages 5315-5319, XP002327477 cited in the application * |
WU G ET AL: "A NOVEL ONE-STEP DIASTEREO- AND ENANTIOSELECTIVE FORMATION OF TRANS-AZETIDINONES AND ITS APPLICATION TO THE TOTAL SYNTHESIS OF CHOLESTEROL ABSORPTION INHIBITORS" JOURNAL OF ORGANIC CHEMISTRY, AMERICAN CHEMICAL SOCIETY. EASTON, US, vol. 64, 1999, pages 3714-3718, XP002296009 ISSN: 0022-3263 cited in the application * |
Cited By (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7470678B2 (en) | 2002-07-05 | 2008-12-30 | Astrazeneca Ab | Diphenylazetidinone derivatives for treating disorders of the lipid metabolism |
US7871998B2 (en) | 2003-12-23 | 2011-01-18 | Astrazeneca Ab | Diphenylazetidinone derivatives possessing cholesterol absorption inhibitory activity |
US7863265B2 (en) | 2005-06-20 | 2011-01-04 | Astrazeneca Ab | 2-azetidinone derivatives and their use as cholesterol absorption inhibitors for the treatment of hyperlipidaemia |
US7893048B2 (en) | 2005-06-22 | 2011-02-22 | Astrazeneca Ab | 2-azetidinone derivatives as cholesterol absorption inhibitors for the treatment of hyperlipidaemic conditions |
US7906502B2 (en) | 2005-06-22 | 2011-03-15 | Astrazeneca Ab | 2-azetidinone derivatives as cholesterol absorption inhibitors for the treatment of hyperlipidaemic conditions |
US8178665B2 (en) | 2005-12-20 | 2012-05-15 | Richter Gedeon Nyrt. | Process for the production of ezetimibe and intermediates used in this process |
US7956182B2 (en) | 2006-02-16 | 2011-06-07 | Kotobuki Pharmaceutical Co., Ltd. | Process for preparing optically active alcohols |
US7842684B2 (en) | 2006-04-27 | 2010-11-30 | Astrazeneca Ab | Diphenylazetidinone derivatives possessing cholesterol absorption inhibitor activity |
US9388440B2 (en) | 2009-04-01 | 2016-07-12 | Mylan Laboratories Limited | Enzymatic process for the preparation of (S)-5-(4-fluoro-phenyl)-5-hydroxy-1morpholin-4-yl-pentan-1-one, an intermediate of Ezetimibe and further conversion to Ezetimibe |
CN107488173A (zh) * | 2016-06-10 | 2017-12-19 | 山东新时代药业有限公司 | 一种依折麦布中间体及其合成方法 |
CN108586373A (zh) * | 2018-06-22 | 2018-09-28 | 苏州市贝克生物科技有限公司 | 依折麦布中间体的合成方法 |
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WO2005066120A3 (fr) | 2008-01-17 |
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